Influence of different peritoneal dialysis fluids on the in vitro activity of fosfomycin against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa

Abstract

Peritonitis is still the main infectious complication among patients on peritoneal dialysis. For treatment of peritoneal dialysis-related peritonitis, the intraperitoneal administration of antibiotics admixed to peritoneal dialysis fluids (PDFs) should be preferred. However, the influence of diverse PDFs on the activity of frequently used antibiotics has been investigated insufficiently. Thus, the present study set out to investigate the in vitro activity of fosfomycin against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus in commercially available PDFs. Time-kill curves in four different PDFs (Dianeal®, Extraneal®, Nutrineal®, and Physioneal®) were performed over 24 h with two different concentrations of fosfomycin (150 and 400 mg/L) and without antibiotics as control. Cation-adjusted Mueller Hinton broth (CA-MHB) was used as a comparator solution. In blank PDFs, bacterial growth of each organism evaluated was reduced when compared to CA-MHB. For S. aureus in blank Physioneal®, a reduction under the limit of detection was observed within 24 h. The activity of fosfomycin was reduced in all PDFs when compared to CA-MHB except for P. aeruginosa in Nutrineal® where the activity of fosfomycin was increased when investigated at 400 mg/L. Against E.coli, bactericidal activity was demonstrated in Extraneal®, Nutrineal®, and Physioneal®. Fosfomycin resistance (MIC > 1024 mg/L) was observed for P. aeruginosa in CA-MHB at both concentrations and in Nutrineal® at 150 mg/L. Fosfomycin is active in PDFs particularly against the frequently isolated enterobacterium E. coli. The choice of the respective PDF considerably influences the microbiological outcome in vitro. Further studies are warranted to investigate the clinical relevance of these findings.

Compatibility of aztreonam in four commercial peritoneal dialysis fluids

“…Decreased antimicrobial activity of aztreonam in vitro, in glucose containing Physioneal, could be explained due reduced growth of P. aerigunosa in this PDF. This phenomenon was already explained in our previous studies 16 . These findings are in parts compatible to an older study by Fuiano et al who reported the effectiveness of aztreonam in combination with cefuroxime for the therapy of PD-associated peritonitis.…”

“…Time-kill curves with P. aeruginosa ATCC 27853 were performed in Physioneal with 2.27% glucose, Nutrineal, Extraneal, and in cation-adjusted Mueller Hinton broth (CA-MHB) as comparator fluid 15 . Bacteria were grown overnight on 5% sheep blood agar plates at 37 °C, suspended in 0.9% sterile saline to a concentration equivalent to a 0.5 McFarland standard, and diluted 1:100 in PDFs or CA-MHB to obtain final inoculums 16 . Aztreonam was added in PDFs and CA-MHB to achieve final concentration of 20 µg/ml (5 × MIC) and incubation followed on an orbital shaker for 24 h at 37 °C.…”

ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment

“…This has been confirmed in a randomised controlled trial comparing once-daily gentamicin dose versus continuous dosing; treatment success and relapse rate did not differ between the two regimens. The once-daily dosing strategy, nevertheless, was associated with lower trough 197,198,199 , MD 20 mg/L 197,200 Fosfomycin 4 g daily 201,202 No data Imipenem/cilastatin 500 mg in alternate exchange 203 LD 250 mg/L, MD 50 mg/L LD: loading dose in mg; MD: maintenance dose in mg; IP: intraperitoneal; APD: automated peritoneal dialysis. a IP ampicillin is not recommended for treatment of enterococcal peritonitis.…”

Traduction française de «Recommandations de l’ ISPD sur la péritonite : Mise à jour 2022 de la prévention et du traitement. »

“…Penicilline G Amoxicilline Ampicilline a Ampicillin/ sulbactam Piperacilline/ tazobactam Ticarcilline/acide clavulanic Pas d'information Pas d'information 4 gm/jour [185] Pas d'information Pas d'information LD 50,000 unit/L, MD 25000unit/L [13] MD 150 mg/L [184] MD 125 mg/L [186] LD 1000 mg/500 mg, MD 133.3 mg/66.7 Mg [187,188] LD 4 gm/0.5 gm, MD 1 gm/0.125 gm [189] LD 3 gm/0.2 gm, MD 300 mg/20 mg/L [190] Autres Aztreonam Ciprofloxacine Clindamycine Daptomycine Fosfomycine Imipenem/cilastatine Ofloxacine Polymyxine B Quinupristine/ dalfopristine Méropénem Teicoplanine Vancomycine 2 gm/jour [191] Pas d'information Pas d'information 300 mg jour [196] 4 g jour [201,202] 500 mg une poche sur deux [203] Pas d'information Pas d'information 25 mg/L une poche sur deux b [205] 500 mg/jour (pour échange long en DPA) [207] 1000 mg/jour (pour échange court en DPCA) [208,209) 15 mg/kg tous les 5 jours [210] 15-30 mg/kg tous les 5-7 jours c [141,212] en DPCA, 15 mg/kg tous les 4 j [213] en DPA LD 500 mg/L192, MD 250 mg/L [192,193] MD 50 mg/L [194] MD 600 mg/poche [195] LD 100 mg/L [197,198,199], MD 20 mg/L [197,200] Pas d'information LD 250 mg/L, MD 50 mg/L [182] LD 200 mg, MD 25 mg/L [204] MD 300,000 unités (30 mg)/poche [188] Pas d'information MD 125 mg/L [206] LD 400 mg/poche, MD 20 mg/L [211,140] LD 20-25 mg/kg, MD 25 mg/L…”